tbuckley/cabot-search huggingface dataset:
P1650: CT PULMONARY ANGIOGRAPHY UTILIZATION IN THE EMERGENCY DEPARTMENT: DIAGNOSTIC YIELD AND ADHERENCE TO CURRENT GUIDELINES
Authors: Abdulrahman Al Raizah, Abdulaziz Alahmari, Alzahraa Almahlawi, Rawaby Alshmmari, Somiah Aljohani, Yousof Al Zahrani, Mohsen Alzahrani, Aymen Hejazi, Ahmed Alaskar
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: In patients with suspected pulmonary embolism (PE), guidelines recommend using clinical decision rules (CDR) to estimate the probability of PE and recommend against imaging testing in patients with a low probability and instead do D-dimer. If D-dimer is negative, no further tests are required. Use of these CDR scores would limit over testing, decrease unnecessary radiation, contrast and cost. In high probability, guidelines recommend proceed with imaging. Aims: The aim is to investigate the patterns of computed tomography pulmonary angiography (CTPA) use and adherence to current guidelines. Methods: A retrospective review of all patients who underwent imaging with CTPA over a 2-year period (from January 1, 2020, through December 31, 2021) in a single adult emergency department of a tertiary teaching hospital was performed. Electronic records were reviewed for all patients. To determine whether PE was the most likely diagnosis for patients’ presentation the modified Wells Score (mWS) was retrospectively calculated for each patient with a high (likely) clinical probability (score > 4) and low (unlikely) clinical probability (score≤ 4) of PE. The physicians were unaware of the result of the CTPA and D-dimer. Patients were excluded if CDR cannot be determined. The D-dimer assay was performed using INNOVANCE - Siemens Healthcare Diagnostics, with a normal value defined as less than 0.5mg/L. Informed consent was waived. Outcomes: 1.Low probability: percentage of potential avoidable imaging defined as imaging in a low clinical probability (score≤ 4) of PE with negative D-dimer. 2.High probability: Rate of unnecessary D-dimer check. 3.Prevalence of PE. Results: A total of 684 CTPA were done. After exclusion, 422 were included. Majority of the patients 337 (79.8%) were low clinical probability (score≤ 4). PE was diagnosed in 22(5.21%) patients. Seventeen of these events happened in the high probability group (20%). A total of 30 (8.9%) met the avoidable CTPA (DD Negative + PE Unlikely) criteria. None of these patients had PE. D-dimer was inappropriately checked in 45 out of 85 (52.9%) High probability group.Summary/Conclusion: This study provides evidence of suboptimal adherence to guidelines. We found that there is over testing of CTPA as evident by the low prevalence rate compared to other studies. Improper use of CTPA can lead to increased radiation exposure and significant health care costs, as well as increased duration of patient stay at the emergency department. Application of a prediction model and use of d-dimer in the appropriate patient population might help safely exclude the presence of PE while promoting cost-effective allocation of resources. Keywords: Venous thromboembolism, Venous thrombosis, Pulmonary embolism, D-dimer
PB1882: BONE MARROW LYMPHOCYTES AND SUBPOPULATION: A NOVEL PROGNOSTIC INDICATOR IN ACUTE MYELOID LEUKEMIA
Authors: Nahla Ibrahim
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients Aims: We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations Methods: Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City. Analysis of BM lymphocytes and subpopulations was done by flow cytometry. Results: Significantly, high percentages of BM lymphocytes, T cells, and natural killer (NK) cells were detected in the group that achieved complete remission (P values = 0.004, <0.001, and <0.001, respectively). Overall survival (OS) was significantly prolonged in patients with high BM lymphocytes and T cells (P values = 0.047 and P 0.002, respectively). Multivariate analysis indicated that BM T-cell percentage and cytogenetics were independent prognostic factors predictive of OS (HR 4.7, P value = 0.011). Summary/Conclusion: BM T-cell percentage constitutes a novel host factor that can be used in combination with cytogenetics to better predict OS. Large-scale multicenter studies are recommended to clarify its role as a predictor of OS and leukemia-free survival. Keywords: Bone Marrow, Acute myeloid leukemia
PB2006: MOLECULAR CLINICAL CHARACTERISTICS AND PROGNOSIS OF MDS PATIENTS WITH RUNX1 MUTATION
Authors: Nanfang Huang, Yang Song, Qi He, Lingyun Wu, Juan Guo, Zheng Zhang, Xiao LI, Chunkang Chang, Feng Xu
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: RUNX transcription factor family members are important in regulating biological processes such as cell proliferation, differentiation and apoptosis. RUNX1 is involved in the mechanism of a variety of solid tumors, and it is also one of the most common mutated genes in hematologic malignancies. The molecular characteristics and prognosis in myelodysplastic syndromes (MDS) patients with RUNX1 mutations need to be further explored. Aims: To investigate the molecular characteristics and prognostic effects of RUNX1 mutations in patients with MDS. Methods: Bone marrow samples from 661 newly diagnosed MDS patients were collected. A series of gene mutations were detected by Next Generation Sequencing (NGS). The clinical characteristics, common mutation expression profile and prognostic significance of patients with RUNX1 mutations were analyzed retrospectively. Results: We found that RUNX1 is mutated in 9.8% of MDS. RUNX1-mutated patients had higher bone marrow blast propotion comparing with RUNX1-wildtype, and were more concentrated in higher-risk groups. 59 of the 65 RUNX1-mutated patients had other gene mutations, and subjects ≥ 60 years carry more mutations than ＜60 years. The most frequently mutated genes in RUNX1-mutated patients were ASXL1, followed by TET2, EZH2 and U2AF1, which mainly involved epigenetic genes and splicing genes. Patients with RUNX1 mutations had a shorter progression-free survival and a higher risk of acute myeloid leukemia (AML) transformation than those without RUNX1 mutations. Summary/Conclusion: RUNX1 mutations occur frequently in MDS patients and usually accompanied by epigenetic gene and splice gene mutations. RUNX1 mutations predicted shorter progression-free survival and higher risk of AML transformation. Molecular clinical characteristics and prognosis of MDS patients with RUNX1 mutation Nanfang Huang1, Yang Song1, Qi He1, Lingyun Wu1, Zheng Zhang1, Juan Guo1, Xiao Li1, Chunkang Chang1, Feng Xu1,* 1Department of Hematology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine *Correspondence to: Feng Xu, MD, PhD, Dept. of Hematology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, 200233 E-mail: [email protected], Tel: +86-021-24058336, Fax: +86-021-64701361 This study was supported by the National Natural Science Foundation of China (Grant No. 81770120 and 81770122) The authors declare no competing financial interests. Keywords: RUNX1, Mutation, MDS
PB1733: LONG-TERM FOLLOW-UP FOR PATIENTS WITH T CELL LYMPHOBLASTIC LYMPHOMA/ ACUTE LYMPHOBLASTIC LEUKEMIA WHO RECEIVED MODIFIED BFM PROTOCOLS
Authors: Yan Gao, Liqin Ping, Xiaoxiao Wang, Bing Bai, Xuanye Zhang, Qingqing Cai, Zhi-Ming LI, Huang He, Liang Yang, Yizhuo Zhang, Huiqiang Huang
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Although the prognosis of lymphoblastic lymphoma (LBL) has significantly improved with the application of intensive acute lymphoblastic leukemia (ALL)-type chemotherapy regimens, there is still no global consensus on the standard first-line therapy for patients with LBL. Aims: In the present study, we aimed to investigate the efficacy and safety of BFM protocols containing pegaspargase in the treatment of T-LBL/ALL patients, especially on long-term outcomes. Methods: In this retrospective study, medical records of patients with T-LBL/ALL who received BFM regimens containing pegaspargase between January 2010 and December 2020 at Sun Yat-Sen University Cancer Center were collected and analyzed. The primary outcome was overall survival (OS); secondary outcomes endpoints were progression free survival (PFS), complete response (CR) rate, and safety. Results: A total of 233 patients were included in this study, of which most patients were diagnosed with LBL, 120 (54%) patients were older than 14 years, and the male-to-female ratio was around 3:1. Overall, 170 patients received modified BFM-90 regimen, while the rest received modified BFM-95 regimen, both containing pegaspargase. Eventually, 195 (87.4%) patients achieved CR, the estimated 5-year PFS was 70.4% (95%CI: 64.2, 77.2), 5-year overall survival reached 75.5% (95% CI: 69.5, 82.1). Univariate analyses showed that older age, bone marrow invasion or central nervous system (CNS) metastasis were associated with worse PFS and OS. The most commonly observed adverse events (AEs) of any grade were white blood cell count decrease (97.3%), followed by anemia (96.9%) and thrombocytopenia (92.4%). Ten (4.5 %) patients died due to treatment-related AEs. Summary/Conclusion: Modified BFM-90 and BFM-95 regimens containing pegaspargase showed an encouraging efficacy and acceptable toxicity in patients with T-LBL/ALL. Further prospective studies are warranted to verify our findings. Keywords: T cell lymphoma, T cell leukemia
PB1855: USE OF MACHINE LEARNING MODEL TO IDENTIFY PATIENTS RECEIVING OPTIMAL TREATMENT AND THE ASSOCIATED NON-BIOLOGICAL FACTORS: A POPULATION-BASED STUDY
Authors: Kueshivi Midodji Atsou, Bernard Rachet, Camille Maringe, Edouard Cornet, Marie Lorraine Chretien, Cedric Rossi, Laurent Remontet, Laurent Roche, Roch Giorgi, Sophie Gauthier, Stéphanie Girard, Johann Böckle, Stephane Wasse, Hélène Rachou, Laila Bouzid, Jean-Marc Poncet, Sébastien Orazio, Alain Monnereau, Xavier Troussard, Marc Maynadie
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: AML patients not admitted to specialised haematology unit (SHU) during their care pathway have less access to curative treatment. Aims: Our aim is to determine whether access to optimal curative treatment is based on the patient’s clinico-biological characteristics or affected by non-biological factors. Methods: Patients were described according to their treatment modalities (curative, non-curative and untreated). In 1000 times bootstrapping process, we trained machine learning (ML) algorithms to learn the clinico-biological characteristics that were used to decide the treatment modalities of AML gold standard patient (treated in academic hospitals by haematologists within 5 days of their diagnosis, n=297). Based on the ML model predictions, we create two groups of patients: optimal treatment patient (predicted as treated and effectively treated) versus non-optimal treatment patients (predicted as treated but effectively untreated). Then after, a multivariate logistic regression model was used to determine the non-biological factors associated with non-optimal treatments. Finally, the mean of the 1000 estimates was used as the Odds Ratio. Results: In our study, 499 patients (n=48.03%), 273 (26.28%) and 261 (25.12%) had respectively received curative, non-intensive and no treatment. The 3 most influential factors in the choice of treatment modalities were age (61.24% influence), secondary aspect of AML/MDS (21.43%) and presence of severe comorbidities (4.95%). In total, n=460 (44.5%) had received optimal treatment and n=101 (9.8%) received non-optimal treatment. Factors associated with non-optimal treatment were: living in Basse-Normandie (0.63 times) and living in a municipality located between 30 and 100km of an academic hospital. Summary/Conclusion: We show that non-biological factors, in particular geographical disparities have an impact on access to optimal curative treatment. This may be related to geographical disparities in the organisation of the AML care pathway or potentially to the situation of a geographical medical desert, which needs to be studied in more detail.Keywords: Artificial intelligence, Population, Acute myeloid leukemia, Epidemiology
PB2544: GAUCHER-LIKE CELLS IN THALASSEMIA INTERMEDIA: IS IT A CHALLENGE?
Authors: Veroniki Komninaka, Pagona Flevari, Georgios Karkaletsis, Theodoros Androutsakos, Theofili Karkaletsi, Ioannis Ntanasis-Stathopoulos, Evaggelia-Eleni Delaki, Evangelos Terpos
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Here we describe a case of a patient diagnosed with thalassemia intermedia (TI) through investigation for the presence of Gaucher like cells in the bone marrow biopsy and also a case of a patient with TI, multiple myeloma (MM) and Gaucher like cells in the bone marrow biopsy. There are limited references in the literature regarding thalassemia intermedia and Gaucher like cells. Aims: To present our experience and to enhance the knowledge on this field. Methods: We describe two cases of thalassemia intermedia (TI) patients with the presence of Gaucher like cells in hematopoietic tissue biopsies. Results: A 56 year old female with bone lesions, splenomegaly, hypochromic microcytic anemia was under investigation and the presence of Gaucher like cells in the bone marrow biopsy led to a diagnostic dilemma. The diagnostic workup excluded Lysosomal Storage Diseases (LSD) and hematological malignancies with a final confirmation of thalassemia intermedia. A 69 year old male with thalassemia intermedia, monoclonal gammopathy of undetermined significance (MGUS), bone disease and Gaucher like cells in the bone marrow and spleen was under investigation for the co-existence of LSD, especially Gaucher Disease (GD). Through further investigations, only heterozygoty of GD was confirmed but the MGUS was accelerated to multiple myeloma requiring treatment. Summary/Conclusion: Gaucher like cells are difficult to differentiate from true Gaucher cells, that are the hallmark of GD suspicion. These cells are usually reported in the lymphohematopoietic system. They have been described in myeloproliferative disorders, hematological malignancies, infectious diseases, hemoglobinopathies and other hemolytic anemias. The presence of Gaucher like cells in patients with thalassemia major has been well-documented, whereas there are limited references regarding cases with thalassemia intermedia. The identification of these cells in thalassemia probably reflects the high cell turnover. The bony complications in GD and TI is not yet fully explained in the literature and this raises the question if Gaucher like cells could play a pathogenetic role in the bone lesions in thalassemia as Gaucher cells are considered to play a similar role in bone complications of GD. Given the rarity and similarity of Gaucher and Gaucher like cells, we would like to highlight that the presence of Gaucher like cells in the bone marrow should not be overlooked as they might be obscuring an underlying pathology, in order to ensure that hematologists, internists and hematopathologists will make a prompt and accurate diagnosis. Keywords: Bone Marrow, Thalassemia, Lysosomal storage disease, Gaucher disease
PB1949: ROLE OF LAIR1 (CD305) IN FLOW CYTOMETRIC DETECTION OF OCCULT BONE MARROW INVOLVEMENT IN NON-CLL B-CELL NON-HODGKIN LYMPHOMA
Authors: Sitaram Ghogale, Anu Singh, Nilesh Deshpande, Karishma Girase, Harshini Sriram, Sweta Rajpal, Gaurav Chatterjee, Nikhil Patkar, Sumeet Gujral, Papagudi G Subramanian, Prashant Tembhare
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Staging of B NHLs is crucial as it provides definitive evidence of stage of disease and is important for making a decision regarding treatment strategy. Bone marrow involvement is a vital part of staging B-NHL. We hypothesized that CD305, also known as LAIR1 (leukocyte immunoglobulin-like receptor-1), is a robust marker for detecting occult bone marrow involvement. LAIR expression varies during various stages of B cell differentiation. Aims: To study role of LAIR1 (CD305) in occult bone marrow involvement of B- cell non-Hodgkin lymphoma by flowcytometry. Methods: CD305(BV78, clone DX26) was incorporated in the lymphoma screening tube used for assessment of bone marrow(BM) involvement as a part of B-NHL staging between January 2020 and December 2021. Occult bone marrow involvement was defined as B-NHL involvement with <10% lymphoma cells. Multicolor Flow cytometric immunophenotyping (MFC) was performed using a 13-color panel on DxFlex flow-cytometer. Data was analyzed using Kaluza-V2.1-software. Results: We studied BM samples from 1084 patients. Of them, 148 cases were clearly involved by morphological/immunophenotypic evaluation. Of the remaining, 172 cases did not reveal morphological involvement and were detected on MFC independently with a median tumor burden of 1.05(0.005-89). Median age was 57 years (range 7-80). These included CD5 positive lymphomas 35/172(20.3%), CD10 positive lymphomas 77/172(44.7%) and CD5, CD10 double-negative lymphomas 60/172, (34.8%). 149/172 (86.6%) cases revealed occult BM involvement. In 93/149 (62.4%) cases, B-NHL cells were identified using the expression-pattern of CD5, CD10, CD11c, CD20, CD38, CD45, and Forward scatter in the background of normal B-cells. In the remaining 48/149(32.2%) cases, the tumor population was identified using only CD305 negative expression. Median (range) of tumor burden was 0.59% (0.016-9.7 %). Overall, CD305 was down-regulated in 155/172(90.1%) cases. CD305 was indispensable in the detection of occult BM involvement in 56(37.6%) cases which, lacked other immunophenotypic abnormalities and was helpful in 99/172(57.6%) samples. Summary/Conclusion: CD305 is a crucial marker in detecting bone marrow involvement in cases of B-cell NHL by MFC, particularly CD5 and CD10 negative lymphomas where detection of minimal BM involvement would be challenging without the incorporation of CD305 in the lymphoma screening panel. It also provides an aberrant expression as an additional abnormality in a significant proportion of samples and provides supporting evidence in the detection of minute tumor populations.Keywords: Bone marrow involvement, Cytometry, Immunophenotype, B cell lymphoma
P1635: DETERMINATION OF THE EFFECTIVE CONCENTRATION OF TRANEXAMIC ACID NEUTRALIZING IN AN IN VITRO UROKINASE INDUCED HYPERFIBRINOLYTIC MODEL USING A GLOBAL FIBRINOLYTIC CAPACITY ASSAY
Authors: Anton Evenepoel, Anne Demulder, Laurence Rozen
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Tranexamic acid (TXA), an anti-fibrinolytic drug, can be used to reduce blood loss and transfusion need in surgery and trauma situations. However, overdosing of TXA can lead to hypofibrinolysis and thus a pro-coagulant state. Previous research has demonstrated the possibility to evaluate the dose-effect response of TXA with thromboelastography. The Lysis timer® (LT), a device developed by Biophen, is designed to determine the global fibrinolysis capacity (GFC) of patients in less than 1 hour. Aims: The aim of our project is to determine the effective concentration (EC) of TXA using the GFC/LT, to facilitate TXA use in surgery or trauma. Methods: Hyperfibrinolysis was induced by spiking citrated plasma with increasing concentration of Actosolv® (urokinase; uPA), from 0 to 5000 UI/mL. Our aim was to determine the optimal uPA concentration able to establish a hyperfibrinolysis model. Once this concentration was established, increasing concentrations of TXA (2.5 µg/mL – 100 µg/mL) were added to the uPA spiked citrated plasmas (n-4), and GFC measured. The EC50% and EC95% were determined using Graphpad Prism. Results: The dose-response curve that allowed us to determine the optimal uPA concentration capable to induce a hyperfibrinolysis model is shown in figure 1a. We chose uPA of 125 U/ml. Next, increasing concentrations of TXA were added to 4 uPA spiked plasmas. The neutralization dose-response curve can be found in figure 1b. We found an EC50% at 12.7 µg/mL TXA and an EC95% at 66.1 µg/mL. Summary/Conclusion: This study highlights the possibility to determine the TXA concentration able to neutralize hyperfibrinolysis in an in vitro setting, with potential clinical applications. We found that a concentration of 12.7 µg/mL TXA was sufficient to inhibit hyperfibrinolysis in 50% of 4 uPA spiked plasmas tested population. This corresponds to similar observations in other studies evaluating the TXA concentration using thromboelastography (Rozen et al, 2015). As the “optimal” TXA concentration required to completely inhibit fibrinolysis remains to be determined in clinic, we think that this method could be used to determine the minimal TXA concentration to inhibit hyperfibrinolysis in different urgent clinical settings (surgery, trauma, post-partum bleeding...). The limitation of our study is the low number of plasmas in our model. Further research is needed to reveal its in vivo applicability.Keywords: Bleeding, Fibrinolysis, Therapy